This invention relates to semisynthetic macrolides, and more particularly to erythromycylamine 11,12-carbonate, its 2'-acetyl-, 2'-propionyl- and 2'-(3-carbethoxypropionyl)- derivatives; to pharmaceutically acceptable acid addition salts thereof; and to methods for their preparation and use as antibacterial agents. Erythromycin A is a macrolide antibiotic produced by fermentation and described in U.S. Pat. No. 2,653,899. Numerous derivatives of erythromycin A have been prepared in efforts to modify its biological and/or pharmacodynamic properties.
Erythromycin A esters with mono- and dicarboxylic acids are reported in Antibiotics Annual, 1953-1954, Proc. Symposium Antibiotics (Washington, D.C.), pages 500-513 and 514-521, respectively. U.S. Pat. No. 3,417,077 describes the cyclic carbonate ester of erythromycin A, the reaction product of erythromycin A and ethylene carbonate, as an active antibacterial agent.
The 9-amino derivative of erythromycin A, known as erythromycylamine, has been extensively investigated and derivatized. Sulfonamide derivatives of erythromycylamine are described in U.S. Pat. No. 3,983,103 as antibacterial agents. N-substituted derivatives of erythromycylamine are reported by Ryden et al., J. Med. Chem., 16, 1059 (1973), and by Witzel, et al., in U.S. Pat. No. 4,016,263 as antibacterial agents for oral or parenteral use. Various aldehyde-erythromycylamine condensation products are described in U.S. Pat. Nos. 3,681,322 and 4,048,306 and Belgian Pat. No. 840,431 as antibacterial agents.
Methods for preparing 9(S)- and 9(R-)-erythromycylamines are described by Massey et al., in Tetrahedron Letters, 157 (1970); Wildsmith, Tetrahedron Letters, 29 (1972); and Massey et al., J. Med. Chem., 17 105-107 (1974).